scholarly journals Molecular spherical nucleic acids

2018 ◽  
Vol 115 (17) ◽  
pp. 4340-4344 ◽  
Author(s):  
Hui Li ◽  
Bohan Zhang ◽  
Xueguang Lu ◽  
Xuyu Tan ◽  
Fei Jia ◽  
...  
Keyword(s):  
Living Cells ◽  
Regulate Gene Expression ◽  
Spherical Nucleic Acid ◽  
Dna Strands ◽  
Nuclease Resistance ◽  
Degree Of Control ◽  
Spherical Nucleic Acids ◽  
Antisense Agent ◽  
Different Levels ◽  
Transfection Agent

Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.

scholarly journals Cockayne Syndrome B protein selectively interacts and resolves intermolecular DNA G-quadruplex structures

2021 ◽  
Author(s):  
Denise Liano ◽  
Marco Di Antonio
Keyword(s):  
Ribosomal Dna ◽  
Living Cells ◽  
Cockayne Syndrome ◽  
Biological Functions ◽  
Loss Of Function ◽  
Endogenous Protein ◽  
G Quadruplex ◽  
Dna Strands ◽  
Low Probability ◽  
Dna Strand

AbstractGuanine-rich DNA can fold into secondary structures known as G-quadruplexes (G4s). G4s can form from a single DNA-strand (intramolecular) or from multiple DNA-strands (intermolecular), but studies on their biological functions have been often limited to intramolecular G4s, owing to the low probability of intermolecular G4s to form within genomic DNA. Herein, we report that the endogenous protein Cockayne Syndrome B (CSB) binds with picomolar affinity to intermolecular G4s, whilst displaying negligible binding towards intramolecular structures. We also observed that CSB can selectively resolve intermolecular G4s in an ATP independent fashion. Our study demonstrates that intermolecular G4s formed within ribosomal DNA are natural substrates for CSB, strongly suggesting that these structures might be formed in the nucleolus of living cells. Given that CSB loss of function elicits premature ageing phenotypes, our findings indicate that the interaction between CSB and ribosomal DNA intermolecular G4s is essential to maintain cellular homeostasis.

scholarly journals Biodegradable DNA-Brush Block Copolymer Spherical Nucleic Acids Enable Transfection Agent-Free Intracellular Gene Regulation

Small ◽  
2015 ◽  
Vol 11 (40) ◽  
pp. 5360-5368 ◽  
Author(s):  
Chuan Zhang ◽  
Liangliang Hao ◽  
Colin M. Calabrese ◽  
Yu Zhou ◽  
Chung Hang J. Choi ◽  
...  
Keyword(s):  
Gene Regulation ◽  
Block Copolymer ◽  
Nucleic Acids ◽  
Spherical Nucleic Acids ◽  
Transfection Agent

Actuation systems in plants as prototypes for bioinspired devices

2009 ◽  
Vol 367 (1893) ◽  
pp. 1541-1557 ◽  
Author(s):  
Ingo Burgert ◽  
Peter Fratzl
Keyword(s):  
Cell Walls ◽  
Cell Shape ◽  
Living Cells ◽  
Polymer Composition ◽  
Plant Cell Walls ◽  
Geometrical Constraints ◽  
Actuation Systems ◽  
Different Levels ◽  
Dead Tissue ◽  
Shape And Size

Plants have evolved a multitude of mechanisms to actuate organ movement. The osmotic influx and efflux of water in living cells can cause a rapid movement of organs in a predetermined direction. Even dead tissue can be actuated by a swelling or drying of the plant cell walls. The deformation of the organ is controlled at different levels of tissue hierarchy by geometrical constraints at the micrometre level (e.g. cell shape and size) and cell wall polymer composition at the nanoscale (e.g. cellulose fibril orientation). This paper reviews different mechanisms of organ movement in plants and highlights recent research in the field. Particular attention is paid to systems that are activated without any metabolism. The design principles of such systems may be particularly useful for a biomimetic translation into active technical composites and moving devices.

scholarly journals Visualizing looping of two endogenous genomic loci using synthetic zinc-finger proteins with anti-FLAG and anti-HA frankenbodies in living cells

2021 ◽  
Author(s):  
Yang Liu ◽  
Ning Zhao ◽  
Masato T Kanemaki ◽  
Yotaro Yamamoto ◽  
Yoshifusa Sadamura ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Signal Amplification ◽  
Fluorescent Proteins ◽  
Close Association ◽  
Zinc Finger Proteins ◽  
Living Cells ◽  
Regulate Gene Expression ◽  
Cohesin Subunit ◽  
Single Living Cells ◽  
Single Living

In eukaryotic nuclei, chromatin loops mediated through cohesin are critical structures that regulate gene expression and DNA replication. Here we demonstrate a new method to visualize endogenous genomic loci using synthetic zinc-finger proteins harboring repeat epitope tags (ZF probes) for signal amplification via binding of tag-specific intracellular antibodies, or frankenbodies, fused with fluorescent proteins. We achieve this in two steps. First, we develop an anti-FLAG frankenbody that can bind FLAG-tagged proteins in diverse live-cell environments. The anti-FLAG frankenbody complements the anti-HA frankenbody, enabling two-color signal amplification from FLAG and HA-tagged proteins. Second, we develop a pair of cell-permeable ZF probes that specifically bind two endogenous chromatin loci predicted to be involved in chromatin looping. By coupling our anti-FLAG and anti-HA frankenbodies with FLAG- and HA-tagged ZF probes, we simultaneously visualize the dynamics of the two loci in single living cells. This reveals close association between the two loci in the majority of cells, but the loci markedly separate upon the triggered degradation of the cohesin subunit RAD21. Our ability to image two endogenous genomic loci simultaneously in single living cells provides a proof-of-principle that ZF probes coupled with frankenbodies are useful new tools for exploring genome dynamics in multiple colors.

scholarly journals Drug-Loaded Liposomal Spherical Nucleic Acid as an Effective Cancer Nanovaccine

2021 ◽  
Author(s):  
Bo Deng ◽  
Bing Ma ◽  
Yingying Ma ◽  
Pei Cao ◽  
Xigang Leng ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Cells ◽  
Tumor Tissue ◽  
Simple Strategy ◽  
Spherical Nucleic Acid ◽  
Animal Survival ◽  
Cpg Oligonucleotides ◽  
Specific Antigens ◽  
Spherical Nucleic Acids ◽  
Mouse Lymphoma

Abstract Background: Cancer nanovaccine has become a promising approach for cancer immunotherapy. The major challenge of cancer vaccines is limited efficacy caused by lack of desirable tumor specific antigens (TSA). Chemotherapeutics can trigger immunogenic cell death (ICD) and release TSAs, which initiate tumor-specific immune responses. However, ICD-triggered immune responses are usually not potent enough to eliminate the tumor cells. Herein, we developed liposomal spherical nucleic acids (SNA) that can simultaneously deliver and release doxorubicin (DOX) and CpG oligonucleotides upon biological stimuli in tumors to augment antitumor immune responses. Results: SNA nanoparticle increased DOX accumulation at the tumor tissue to induce tumor cells apoptosis and autophagy to activate both ICD-triggered and autophagy-mediated Th1-type immune responses. Meanwhile, CpG, which was co-delivered with DOX, functioned synergistically to potentiate the antitumor immune responses. These nanoparticles effectively inhibited tumor growth and extended animal survival of a mouse lymphoma model. Conclusions: This work provided a simple strategy of delivering chemotherapeutics and adjuvants to tumors to improve immunotherapeutic efficacy of nanovaccines.

A spherical nucleic acid-based two-photon nanoprobe for RNase H activity assay in living cells and tissues

Nanoscale ◽  
2019 ◽  
Vol 11 (17) ◽  
pp. 8133-8137 ◽  
Author(s):  
Ningning Wang ◽  
Liran Song ◽  
Hang Xing ◽  
Ke Zhang ◽  
Ronghua Yang ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Gold Nanoparticle ◽  
Ex Vivo ◽  
Living Cells ◽  
Rnase H ◽  
Activity Assay ◽  
Two Photon ◽  
Spherical Nucleic Acid ◽  
Nanoparticle Core

We report here a two-photon nanoprobe for the detection of RNase H activity in living cells andex vivotissues by combining a two-photon dye with a spherical nucleic acid (SNA) featuring a DNA/RNA duplex corona and a gold nanoparticle core.

Transdermal Delivery of Poly-Hyaluronic Acid-Based Spherical Nucleic Acids for Chemogene Therapy

Nanoscale ◽  
2022 ◽  
Author(s):  
Kai Jiang ◽  
Di Zhao ◽  
Rui Ye ◽  
Xinlong Liu ◽  
Chao Gao ◽  
...  
Keyword(s):  
Hyaluronic Acid ◽  
Nucleic Acid ◽  
Gene Delivery ◽  
Nucleic Acids ◽  
Delivery System ◽  
Transdermal Delivery ◽  
Gene Delivery System ◽  
Transdermal Administration ◽  
Spherical Nucleic Acid ◽  
Spherical Nucleic Acids

Spherical nucleic acid (SNA), as a good gene delivery system, has a good application prospect for transdermal administration in skin disorders treatment. However, most of traditional SNA core materials are...

scholarly journals A multiplexed, automated evolution pipeline enables scalable discovery and characterization of biosensors

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Brent Townshend ◽  
Joy S. Xiang ◽  
Gabriel Manzanarez ◽  
Eric J. Hayden ◽  
Christina D. Smolke
Keyword(s):  
Small Molecules ◽  
Biosynthetic Pathway ◽  
De Novo ◽  
Living Cells ◽  
Regulate Gene Expression ◽  
Liquid Handling ◽  
Regulate Gene

AbstractBiosensors are key components in engineered biological systems, providing a means of measuring and acting upon the large biochemical space in living cells. However, generating small molecule sensing elements and integrating them into in vivo biosensors have been challenging. Here, using aptamer-coupled ribozyme libraries and a ribozyme regeneration method, de novo rapid in vitro evolution of RNA biosensors (DRIVER) enables multiplexed discovery of biosensors. With DRIVER and high-throughput characterization (CleaveSeq) fully automated on liquid-handling systems, we identify and validate biosensors against six small molecules, including five for which no aptamers were previously found. DRIVER-evolved biosensors are applied directly to regulate gene expression in yeast, displaying activation ratios up to 33-fold. DRIVER biosensors are also applied in detecting metabolite production from a multi-enzyme biosynthetic pathway. This work demonstrates DRIVER as a scalable pipeline for engineering de novo biosensors with wide-ranging applications in biomanufacturing, diagnostics, therapeutics, and synthetic biology.

scholarly journals A DNA-mediated crosslinking strategy to enhance cellular delivery and sensor performance of protein spherical nucleic acids

2021 ◽  
Author(s):  
Jing Yan ◽  
Ya-Ling Tan ◽  
Min-jie Lin ◽  
Hang Xing ◽  
Jian-Hui Jiang
Keyword(s):  
Signal To Noise Ratio ◽  
Supramolecular Architecture ◽  
Cellular Delivery ◽  
Signal To Noise ◽  
Intracellular Enzyme ◽  
Sensor Performance ◽  
Spherical Nucleic Acid ◽  
Spherical Nucleic Acids ◽  
Enzyme Delivery ◽  
Delivery Efficiency

By crosslinking protein spherical nucleic acid (SNA) into a supramolecular architecture X-SNA, the intracellular enzyme delivery efficiency was significantly enhanced, showing 3–4 times higher signal-to-noise ratio in detecting intracellular lactate.

scholarly journals The Distinct Function and Localization of METTL3/METTL14 and METTL16 Enzymes in Cardiomyocytes

2020 ◽  
Vol 21 (21) ◽  
pp. 8139
Author(s):  
Orazio Angelo Arcidiacono ◽  
Jana Krejčí ◽  
Eva Bártová
Keyword(s):  
Cell Differentiation ◽  
Trichostatin A ◽  
Hdac Inhibitors ◽  
Embryonic Stem ◽  
Distribution Patterns ◽  
Wild Type ◽  
Immunofluorescence Analysis ◽  
Down Regulation ◽  
Regulate Gene Expression ◽  
Different Levels

It has become evident that epitranscriptome events, mediated by specific enzymes, regulate gene expression and, subsequently, cell differentiation processes. We show that methyltransferase-like proteins METTL3/METTL14 and N6-adenosine methylation (m6A) in RNAs are homogeneously distributed in embryonic hearts, and histone deacetylase (HDAC) inhibitors valproic acid and Trichostatin A (TSA) up-regulate METTL3/METTL14 proteins. The levels of METTL3 in mouse adult hearts, isolated from male and female animals, were lower in the aorta and pulmonary trunks when compared with atria, but METT14 was up-regulated in the aorta and pulmonary trunk, in comparison with ventriculi. Aging caused METTL3 down-regulation in aorta and atria in male animals. Western blot analysis in differentiated mouse embryonic stem cells (mESCs), containing 10–30 percent of cardiomyocytes, showed METTL3/METTL14 down-regulation, while the differentiation-induced increased level of METTL16 was observed in both wild type (wt) and HDAC1 depleted (dn) cells. In parallel, experimental differentiation in especially HDAC1 wild type cells was accompanied by depletion of m6A in RNA. Immunofluorescence analysis of individual cells revealed the highest density of METTL3/METTL14 in α-actinin positive cardiomyocytes when compared with the other cells in the culture undergoing differentiation. In both wt and HDAC1 dn cells, the amount of METTL16 was also up-regulated in cardiomyocytes when compared to co-cultivated cells. Together, we showed that distinct anatomical regions of the mouse adult hearts are characterized by different levels of METTL3 and METTL14 proteins, which are changed during aging. Experimental cell differentiation was also accompanied by changes in METTL-like proteins and m6A in RNA; in particular, levels and distribution patterns of METTL3/METTL14 proteins were different from the same parameters studied in the case of the METTL16 protein.

Sign in / Sign up

Export Citation Format

Share Document